key: cord-1015088-n4aqjolb
authors: Blain, Hubert; Tuaillon, Edouard; Gamon, Lucie; Pisoni, Amandine; Miot, Stéphanie; Picot, Marie-Christine
title: Strong decay of SARS-CoV-2 spike antibodies after two BNT162b2 vaccine doses and high antibody response to a third dose in nursing home residents
date: 2022-02-23
journal: J Am Med Dir Assoc
DOI: 10.1016/j.jamda.2022.02.006
sha: ba4c258695e33f2584c760203efd8744a65e9ade
doc_id: 1015088
cord_uid: n4aqjolb

Objectives To measure the antibody decay after two BNT162b2 doses and the antibody response after a third vaccine dose administered 6 months after the second one in nursing home residents with and without prior COVID-19. Design Cohort study. Setting and Participants 418 residents from 18 nursing homes. Methods Blood RBD-IgG (IgG II Quant assay, Abbott Diagnostics; upper limit: 5680 BAU) and nucleocapsid-IgG (Abbott Alinity) were measured 21-28 days after the second BNT162b2 dose, as well as 1-3 days before and 21-28 days after the third vaccine dose. RBD-IgG levels ≥ 592 BAU/mL were considered as high antibody response. Residents with prior positive RT-qPCR on a nasopharyngeal swab or with N-IgG levels above 0.8 S/CO were considered as prior COVID-19 residents. Results In prior COVID-19 residents (n=122), RBD-IgG median levels decreased by 82% in 167 days on average. In the same period, the number of residents with a high antibody response decreased from 88.5% to 54.9% (p<.0001) and increased to 97.5% after the third vaccine dose (p=0.02 vs the first measure). In residents without prior COVID-19 (n=296), RBD-IgG median levels decreased by 89% in 171 days on average. The number of residents with a high antibody response decreased from 29.4 to 1.7% (p<.0001) and increased to 88.4% after the third vaccine dose (p<.0001 vs the first measure) Conclusions and Implications The strong and rapid decay of RBD-IgG levels after the second BNT162b2 dose in all residents and the high antibody response after the third dose validate the recommendation of a third vaccine dose in residents less than 6 months after the second dose, prioritizing residents without prior COVID-19. The slope of RBD-IgG decay after the third BNT162b2 dose and the protection level against SARS-CoV-2 B.1.1.529 (omicron) and other variants of concern provided by the high post-boost vaccination RBD-IgG response require further investigation in residents.

Nursing home (NH) residents are at high risk for severe COVID-19. Vaccination using the 29 mRNA COVID-19 vaccine is safe and effective in adults but is less documented in older 30

persons. [1] [2] [3] The humoral response observed in NH residents 21 days after the first BNT162b2 31 vaccine dose 4 , and 14 days 5,6 and 6 months following the second vaccine dose, 7-9 has been 32 shown to be lower than that observed in healthcare professionals. In addition, outbreaks of the 33 SARS-CoV-2 variants B.1.1. 4-7 (alpha) and B.1.617.2 (delta) have been reported in nursing 34 homes (NHs) less than 6 months after the full BNT162b2 vaccination of most residents. 8, 11 The 35 low humoral response observed after two BNT162b2 doses, associated with reduced vaccine 36 protection some months after the second vaccine dose, has led to recommendations in the US and 37

in other countries such as France of an additional vaccine dose at last 5 months after the second 38 vaccine dose in persons moderately or severely immunocompromised. 12,13 In France, more than 39 95% of residents had received a second BNT162b2 dose in September 2021. 14 40

The 6-month post-vaccine antibody decay after the second vaccine dose and the antibody 41 response to the third dose have not been quantified in the same NH residents, which does not 42 enable the comparison of the antibody response after 2 and 3 BNT162b2 doses. 43

We compared IgG levels against the SARS-CoV-2 Receptor-Binding Domain (RBD-IgG) (i) 44 after two doses of BNT162b2, (ii) just before the third vaccine dose, and (iii) after the third dose. 45

We distinguished those with and without prior COVID-19. performed 21-28 days after the second vaccine dose, as well as 1-3 days before and 21-28 days 55 after the third dose, to assess RBD-IgG (IgG II Quant assay, Abbott Diagnostics; upper limit: 56 5680 BAU) and nucleocapsid-IgG (Abbott Alinity). RBD-IgG levels < 149 BAU/mL or ≥ 592 57 BAU/mL were considered as low or high responses, respectively. 15, 16 Residents with a history of 58 positive RT-qPCR on a nasopharyngeal swab or with N-IgG levels above 0.8 S/CO were 59 considered as prior COVID-19 residents. All participants (or their legal representative) provided 60 informed consent. The study was approved by our University Hospital institutional review board. 61 RBD-IgG levels were compared by using the Friedman and Cochran tests, and the multinomial 62 mixed model for repeated measures. The statistical significance threshold was set at 5%. 63

Analyses were performed using the SAS Enterprise Guide, v7.3 (SAS Institute Inc). 64

The characteristics of the residents included in the 15 nursing homes are shown in Table 1 . Of 66 the 418 studied residents, 296 had no previous COVID-19 infection (mean age 88 ± 8 years, 74% 67 women), and 122 had prior COVID-19 (88.6 ± 8 years, 81% women). The mean lapse of time 68 between the first and the second RBD-IgG measures were 171 ± 11 and 167 ± 11 days, 69 respectively. 70

In prior COVID-19 residents, RBD-IgG median levels decreased by 82% between the first and 71 second measures (4,318 BAU/mL to 773 BAU/mL), and the number of residents with a high 72 J o u r n a l P r e -p r o o f antibody response decreased from 88.5% to 54.9% (p<.0001). After the third dose, RBD-IgG 73 median levels increased significantly (to 3,596 BAU/mL), and the number of residents with a 74 high RBD-IgG level was higher after the third and after the second dose (97.5% vs 88.5%, 75 respectively)(p=0.02)(Table 2, Figure) . 76

In residents without prior COVID-19, RBD-IgG median levels between the first and second 77 measures decreased by 89% (348 BAU/mL to 35 BAU/mL), and the number of residents with a 78 high antibody response decreased from 29.4% to 1.7% (p<.0001). After the third vaccine dose, 79 88.4% of residents had a high antibody response vs 29.4% after the second dose, and 4.7% had a 80 low antibody response vs 27.4% (p<.0001)(Table, Figure) . BNT162b2 dose at least 5 months after the second one in NH residents. The RBD-IgG response 91 after 3 vaccine doses is significantly higher than that observed after two doses, and is excellent, 92 largely above 592 BAU, in 97.5% of the residents with prior COVID-19 and in 88.4% of those 93 without. Limitations of the study include the relatively small sample size, with a possible lack of 94 representativeness, and the lack of clinical data in residents with prior COVID-19. Whether the 95 severity of the initial infection has impacted the antibody response to the vaccine cannot be 96 analyzed in this study. One other limitation is the lack of neutralization assays. However, we used 97 an automated quantitative assay to measure the RBD IgG level that correlates well with virus 98 neutralization. 17, 18 We did not assess T-cell contribution to vaccine-induced immunity. The present 99 study focuses on antibodies and not on clinical disease. Even if associations have been shown 100 between RBD-IgG levels and protection against SARS-CoV-2 in healthcare workers and NH 101 residents 8,11, 19-21 , whether the high level of RBD IgG found after a booster BNT162b2 dose in 102 most residents is associated with high protection against COVID-19 remains to be determined. 103

Because the administration of a booster BNT162b2 dose as well as the vaccination of previously 104 infected individuals generate an anti-B.1.1.529 neutralizing response, with titers 5 to 31 fold lower 105 against Omicron than against Delta, 22 further studies are needed to assess whether the high RBD-106

IgG response found in most of the residents after the third vaccine dose will be sufficient to prevent 107 SARS-CoV-2 B.1.1.529 in those with and without prior COVID-19 and, if so, for what duration. 108

The strong and rapid decay of RBD-IgG levels 6 months after the second BNT162b2 dose 110 observed in most of the residents (with very low levels observed after the second dose in 111 residents without prior COVID-19), as well as the high antibody response after the third dose in 112 the residents (observed in the present study and in a recent unpublished study) 23 support, on an 113 immunological basis, the recommendation to offer a third vaccine dose in nursing home residents 114 less than at least 5 months after the second dose, prioritizing those without prior COVID-19. 115

Whether the slope of RBD-IgG decay after the third BNT162b2 dose will be similar to that 116 found after the second vaccine dose, and whether the high RBD-IgG response found after the 117 third vaccine dose will be associated with a high protection level against SARS-CoV-2 B.1.1.529 118 and other variants of concern require further investigation in nursing home residents. 

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